Abstract: Nearly 50% of allogeneic hematopoietic cell transplantation recipients (AlloHCT) will develop chronic graft- versus-host disease (cGVHD). Oral involvement is seen in approximately 80% of patients with cGVHD. It presents as mucosal lesions mimicking lichen planus, hyposalivation, and trismus. Low-level evidence suggests that oral cGVHD is associated with increased risk for dental, periodontal, and mucosal diseases. The current oral health guidelines for cGVHD are largely based on expert opinion. Little evidence exists to guide treatment decisions or to personalize management plans. The short-term objective of this application is to address the important gaps of knowledge described above and generate a rationale for establishing an evidence-based approach in the management of patients with oral cGVHD. Our hypothesis is that exposure to oral cGVHD leads to increased tooth loss and that recalcitrant oral cGVHD decreases oral-health-related quality of life (OHRQL) (secondary endpoint), an effect which we hypothesize is mediated by mucosal sensitivity, reduced salivary flow, and trismus. We will utilize the on-going collaboration between the Fred Hutchinson Cancer Research Center (FHCRC) and the Dana-Farber Cancer Institute (DFCI), two key sites of the NIH-funded cGVHD Consortium and nest our studies in a large established population-based cohort. First, we will determine tooth loss rates and OHRQL in AlloHCT recipients and explore their association with oral cGVHD. Subjects in an established and representative cohort of the Chronic GVHD Consortium will be recruited in a retrospective cohort. They will undergo an oral examination by a calibrated examiner. Tooth loss will be evaluated by comparing current status to data collected at the pre-AlloHCT oral examination. OHRQL will be measured through a validated tool (OHIP14). Current and past oral cGVHD status (per NIH criteria) will be assessed through mucosal examination and through Consortium data. We will test for associations between exposure to cGVHD (number of visits with oral cGVHD), tooth loss, and OHRQL. Secondary analysis will assess other risk factors associated with tooth loss and lower OHRQL. Second, we will evaluate the association between recalcitrant oral cGVHD and OHRQL. Subjects with past (exposed) and current oral cGVHD will be enrolled in a prospective cohort and re-evaluated twice per year as in Aim#1. They will receive a comprehensive oral examination including mucosal and periodontal health, caries, and tooth loss. Patient reported outcomes will be measured with validated tools. Additionally, information will be collected from each subjects' primary dentist including number of visits, dental procedures, oral hygiene instructions, fluoride supplementation, and use of sialogogues/ salivary substitutes. We will explore associations between OHRQL and cGVHD, expecting the presence and intensity of oral cGVHD to be associated with lower OHRQL. Secondary analysis will assess additional mediating factors.